4.6 Article

Molecular Associations and Clinical Significance of RAPs in Hepatocellular Carcinoma

Journal

FRONTIERS IN MOLECULAR BIOSCIENCES
Volume 8, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fmolb.2021.677979

Keywords

hepatocellular carcinoma; liver; RAP; TCGA; prognosis; biomarker 3

Funding

  1. Council of Scientific and Industrial Research, Government of India
  2. Department of Health Research, Government of India
  3. Department of Biotechnology, Government of India

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The study found that the RAP gene family is dysregulated in hepatocellular carcinoma, with RAP2A showing the strongest ability to differentiate tumors and being associated with tumor progression, gene mutations, and DNA methylation. RAP2A can also serve as an independent prognostic marker for patients. Additionally, pathway analysis revealed associations between RAP2A expression and tumor-infiltrating immune cells and oncogenic molecular pathways.
Hepatocellular carcinoma (HCC) is an aggressive gastrointestinal malignancy with a high rate of mortality. Multiple studies have individually recognized members of RAP gene family as critical regulators of tumor progression in several cancers, including hepatocellular carcinoma. These studies suffer numerous limitations including a small sample size and lack of analysis of various clinicopathological and molecular features. In the current study, we utilized authoritative multi-omics databases to determine the association of RAP gene family expression and detailed molecular and clinicopathological features in hepatocellular carcinoma (HCC). All five RAP genes were observed to harbor dysregulated expression in HCC compared to normal liver tissues. RAP2A exhibited strongest ability to differentiate tumors from the normal tissues. RAP2A expression was associated with progressive tumor grade, TP53 and CTNNB1 mutation status. Additionally, RAP2A expression was associated with the alteration of its copy numbers and DNA methylation. RAP2A also emerged as an independent marker for patient prognosis. Further, pathway analysis revealed that RAP2A expression is correlated with tumor-infiltrating immune cell composition and oncogenic molecular pathways, such as cell cycle and cellular metabolism.

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